Lymphatic endothelial cell-secreted CXCL1 stimulates lymphangiogenesis and metastasis of gastric cancer
Jianbo Xu
Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Gastric Cancer Center of Sun Yat-Sen University, Guangzhou, China
J.X. and C.Z. contributed equally to this work.
Search for more papers by this authorChanghua Zhang
Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Gastric Cancer Center of Sun Yat-Sen University, Guangzhou, China
J.X. and C.Z. contributed equally to this work.
Search for more papers by this authorCorresponding Author
Yulong He
Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Gastric Cancer Center of Sun Yat-Sen University, Guangzhou, China
Tel.: +86 20 88263393, Fax: +86 20 87331059
Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaSearch for more papers by this authorHui Wu
Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Gastric Cancer Center of Sun Yat-Sen University, Guangzhou, China
Search for more papers by this authorZhao Wang
Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Gastric Cancer Center of Sun Yat-Sen University, Guangzhou, China
Search for more papers by this authorWu Song
Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Gastric Cancer Center of Sun Yat-Sen University, Guangzhou, China
Search for more papers by this authorWen Li
Laboratory of surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Search for more papers by this authorWeiling He
Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Gastric Cancer Center of Sun Yat-Sen University, Guangzhou, China
Search for more papers by this authorShirong Cai
Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Gastric Cancer Center of Sun Yat-Sen University, Guangzhou, China
Search for more papers by this authorWenhua Zhan
Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Gastric Cancer Center of Sun Yat-Sen University, Guangzhou, China
Search for more papers by this authorJianbo Xu
Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Gastric Cancer Center of Sun Yat-Sen University, Guangzhou, China
J.X. and C.Z. contributed equally to this work.
Search for more papers by this authorChanghua Zhang
Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Gastric Cancer Center of Sun Yat-Sen University, Guangzhou, China
J.X. and C.Z. contributed equally to this work.
Search for more papers by this authorCorresponding Author
Yulong He
Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Gastric Cancer Center of Sun Yat-Sen University, Guangzhou, China
Tel.: +86 20 88263393, Fax: +86 20 87331059
Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, ChinaSearch for more papers by this authorHui Wu
Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Gastric Cancer Center of Sun Yat-Sen University, Guangzhou, China
Search for more papers by this authorZhao Wang
Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Gastric Cancer Center of Sun Yat-Sen University, Guangzhou, China
Search for more papers by this authorWu Song
Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Gastric Cancer Center of Sun Yat-Sen University, Guangzhou, China
Search for more papers by this authorWen Li
Laboratory of surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Search for more papers by this authorWeiling He
Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Gastric Cancer Center of Sun Yat-Sen University, Guangzhou, China
Search for more papers by this authorShirong Cai
Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Gastric Cancer Center of Sun Yat-Sen University, Guangzhou, China
Search for more papers by this authorWenhua Zhan
Department of Gastrointestinal Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
Gastric Cancer Center of Sun Yat-Sen University, Guangzhou, China
Search for more papers by this authorAbstract
Lymph node metastasis is a significant factor in gastric cancer prognosis. It is well known that cancer cells secrete lymphangiogenic factors, thereby promoting lymphangiogenesis. However, the effects of lymphatic endothelial cell (LEC)-secreted factors on the process of lymphangiogenesis and tumor cell metastasis remain unclear. We established an animal model and successfully isolated LECs from afferent lymph vessels of sentinel lymph nodes (SLNs) in animal models. A microarray analysis was performed to characterize gene expression profile in afferent LECs induced by metastatic cancer cells. There were significant differences in 846 genes between normal LECs and LECs with lymph node metastasis. Among these genes, we found that expression of CXCL1 was upregulated, which was confirmed by quantitative reverse-transcriptase polymerase chain reaction. In a coculture system, gastric cancer cells induced CXCL1 secretion from LECs, which was associated with the NF-κB pathway. CXCL1 stimulated LECs migration and tube formation involving FAK-ERK1/2-RhoA activation and reorganization of F-actin. In human gastric cancer specimens, CXCR2 expression was positively correlated with TNM (Tumor, node, metastasis) stage and lymphatic vessel density. These results suggested that LECs of afferent SLNs had specific expression profiles, which were distinct from those of normal lymphatic vessels and appeared to promote metastasis. The expression pattern described in our study, including CXCL1 in LECs and its receptor CXCR2 in cancer cells, offers a promising therapeutic target for gastric cancer.
Supporting Information
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